Newborn Screening ACT Sheet

FE (HbEE or HbE/Beta Zero Thalassemia)

EE or Hb E/β0 Disease
Differential Diagnosis: Hemoglobin FE pattern on newborn screen is highly suggestive of homozygous
hemoglobin E or hemoglobin E/beta zero (β0) thalassemia.

Condition Description: A red blood cell disorder characterized on the newborn screen by presence of fetal
hemoglobin (F) and hemoglobin E in the absence of hemoglobin A. The hemoglobins are listed in order of the
amount of hemoglobin present (F> E).

You Should Take the Following Actions

• Contact the family to inform them of the screening result.
• Evaluate infant, assess for splenomegaly, and do complete blood count (CBC) for Hb, and
mean corpuscular volume (MCV) at the initial visit and at six months to differentiate
hemoglobin EE from hemoglobin E/beta zero thalassemia.
• Contact a pediatric hematologist to determine need for further testing.
• Initiate timely confirmatory/diagnostic testing as recommended by consultant.
• Report findings to newborn screening program

Diagnostic Evaluation: CBC and MCV. Hemoglobin separation by electrophoresis, isoelectric focusing
(IEF), or high performance liquid chromatography (HPLC), which shows FE pattern. DNA studies will usually
confirm genotype.

Clinical Considerations: Hemoglobin EE is clinically benign. Individuals with Hb EE are not anemic, but
have microcytosis and target cells on blood smear. Clinical expression of Hb E/β0 thalassemia is variable.
Most individuals with Hb E/β0 thalassemia have moderately severe anemia, hepatosplenomegaly, intermittent
jaundice, growth retardation, and overexpansion of the bone marrow. Severely affected individuals require
lifelong transfusion, splenectomy and treatment for iron overload.

Additional Information:
American College of Medical Genetics and Genomics website
https://www.acmg.net/StaticContent/ACT/Hb_(FE).pdf

Utah Department of Health

http://health.utah.gov/newbornscreening/Disorders/HB/Hb_E_Disease_EE/FactSheet_Provider_HbEE_En.pdf

Hemoglobin Disorders (Grady Comprehensive Sickle Cell Center)

http://scinfo.org/additional-online-books-and-articles/hemoglobins-what-the-results-mean

Thalassemias
http://kidshealth.org/parent/medical/heart/thalassemias.html

Genetics Home Reference

http://ghr.nlm.nih.gov/condition/beta-thalassemia

Disclaimer: This information is adapted from American College of Medical Genetics and Genomics (ACMG) 05/2015
 Newborn Screening FACT Sheet
FE (HbEE or HbE/Beta Zero Thalassemia)
EE or Hb E/β0 Disease
What is Hemoglobin?
Hemoglobin is a protein in the red blood cells. It carries
oxygen from the lungs to all parts of the body and gives
blood its red color. There are many hemoglobin types
(this is not the same as a blood type). Hemoglobin is
inherited through genes, one from each parent. Most
people have hemoglobin A, also called adult
hemoglobin.
What is Hemoglobin E Disease (EE)?
Hemoglobin E in the red blood cells is responsible for
causing hemoglobin E condition (EE). Children inherit
this condition from their parents as a recessive genetic
disorder. This means a hemoglobin E gene is passed
from both mom and dad to the baby causing EE.
Persons with EE have only hemoglobin E and no adult
hemoglobin. When both parents have one hemoglobin E
gene, there is a 1 in 4 or 25% chance with each
pregnancy that an infant will inherit two hemoglobin E
genes. There are no serious health problems associated
with EE, but the gene for hemoglobin E is passed on
from your child to your future grandchildren. EE is not
contagious. Most people with EE have mild anemia and
occasionally may have a slightly enlarged spleen, but
usually they do not have disease symptoms and do not
require treatment. Persons with EE have red blood cells
that are smaller than normal and have an irregular shape.
What Problems can EE Cause?
EE red blood cells are not very flexible in moving
through blood vessels and have a smaller outside
surface area to carry oxygen. EE red blood cells are very
small, unstable and have a reduced ability to hold onto
oxygen. The lifespan of these red blood cells is also
slightly shorter than normal (normal blood cells live
about 120 days).
What is the Frequency of EE?
EE affects both sexes equally and is the second most
common abnormal hemoglobin in the world. It is very
common among persons from Southeast Asia or have
ancestors from Cambodia, Laos and Thailand. EE is
also found in people who live in Vietnam, Malaysia,
northeastern India, Bangladesh, Pakistan and Sri Lanka
and their descendants.
Disclaimer: This information is adapted from Utah Department of Health
What can be done to treat EE?
Treatment is usually not necessary. Folic acid
supplements may be prescribed by your child’s doctor
to help his or her body to produce normal red blood
cells and improve the symptoms of anemia. People with
hemoglobin E disease can expect to lead a normal life.
What is Hemoglobin E/Beta Zero Thalassemia
Disease?
Hemoglobin E/beta-thalassemia disease is a more
serious disease than EE. Children with hemoglobin
E/beta-thalassemia inherit one gene for hemoglobin E
from one parent and one beta-thalassemia gene from the
other parent. The beta-thalassemia gene causes the body
to make less than the normal amount of hemoglobin.
Persons who are affected may have a more severe
anemia which can be life threatening, depending on the
severity of the beta-thalassemia. If not treated, this
disease can lead to heart failure from the severe
destruction of red blood cells. It also can lead to severe
enlargement of the spleen and liver, changes in bones
and poor growth. Treatment may include repeated blood
transfusions. Your baby’s doctor will do a complete
blood count (CBC) and smear of the red blood cells to
look for beta-thalassemia when your baby is
approximately 6 to 9 months of age.
What are the Most Important Things to Remember
about EE and Hemoglobin E/Beta-Thalassemia
Diseases?
Work very closely with your child’s doctor and
hematologist (a doctor who is a blood specialist). Make
sure your child has regular checkups with them. Call
your child’s doctor when you have questions and have
your child seen if you have any medical concerns.
How Do I Get More Information about Hemoglobin
E Disease?
Talk with your baby’s doctor. You may also want to
have a genetic consultation for you and your family to
see how these diseases might affect future children or
grandchildren.
05/2015